Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of dexmedetomidine hydrochloride degradation impurity

A technology of dexmedetomidine hydrochloride and dexmedetomidine is applied in the field of preparation of dexmedetomidine hydrochloride to degrade impurities, achieving the effects of reducing side reactions, low production cost and high safety

Inactive Publication Date: 2021-10-29
HEBEI GUOLONG PHARMA CO LTD
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The compound shown in formula (I) is the degraded impurity (impurity A) of dexmedetomidine hydrochloride, there is no bibliographical report effective synthetic method at present, but as the more important degraded impurity of dexmedetomidine hydrochloride in quality research and High attention should be paid to preparation research

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of dexmedetomidine hydrochloride degradation impurity
  • Preparation method of dexmedetomidine hydrochloride degradation impurity
  • Preparation method of dexmedetomidine hydrochloride degradation impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] This embodiment provides a preparation method for degrading impurities by dexmedetomidine hydrochloride, comprising the following steps:

[0044] Step 1: Dissolve 20.1 g of dexmedetomidine in 140 mL of acetic acid, then add 46.2 g of NaBO 3 4H 2 O, temperature control and stirring reaction at 50° C. for 15 h to obtain a reaction solution containing the degraded impurities shown in formula (I);

[0045] Step 2: The temperature of the reaction solution was lowered to 20°C, 101mL of water and 140mL of ethyl acetate were added, stirred for 15min until uniform, the organic phase was collected after standing and liquid separation, and then the organic phase was dried over anhydrous sodium sulfate , and concentrated at a temperature of 40°C and a vacuum of 0.09MPa to obtain a crude product of degraded impurities. Finally, the crude product of degraded impurities was subjected to silica gel column chromatography (Jiangsu Lianhua Glass Instruments, a chromatography of 40mm×500m...

Embodiment 2

[0048] This embodiment provides a preparation method for degrading impurities by dexmedetomidine hydrochloride, comprising the following steps:

[0049] Step 1: Dissolve 20.1 g of dexmedetomidine in 101 mL of acetic acid, then add 92.4 g of NaBO 3 4H 2 O, temperature control and stirring reaction at 60° C. for 12 hours to obtain a reaction solution containing the degraded impurities shown in formula (I);

[0050] Step 2: The temperature of the reaction solution was lowered to 25°C, 161mL of water and 201mL of ethyl acetate were added, stirred for 20min until uniform, the organic phase was collected after standing and liquid separation, and then the organic phase was dried over anhydrous sodium sulfate , and at a temperature of 45° C. and a vacuum of 0.10 MPa, concentrate to obtain a crude product of degraded impurities. Finally, the crude product of degraded impurities is subjected to silica gel column chromatography (Jiangsu Lianhua Glass Instruments, with a specification of...

Embodiment 3

[0053] This embodiment provides a preparation method for degrading impurities by dexmedetomidine hydrochloride, comprising the following steps:

[0054] Step 1: Dissolve 20.1g of dexmedetomidine in 201mL of acetic acid, then add 61.5g of NaBO 3 4H 2 O, temperature control and stirring reaction at 55° C. for 15 h to obtain a reaction solution containing degraded impurities shown in formula (I);

[0055] Step 2: Cool the reaction solution to 30°C, add 201mL of water and 101mL of ethyl acetate, stir for 10min until uniform, let stand, and collect the organic phase after liquid separation, and then dry the organic phase over anhydrous sodium sulfate , and concentrated at a temperature of 42°C and a vacuum of 0.09MPa to obtain a crude product of degraded impurities. Finally, the crude product of degraded impurities was subjected to silica gel column chromatography (Jiangsu Lianhua Glass Instruments, a 40mm×500mm chromatography Column), carry out gradient elution with the volume r...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the technical field of medicine synthesis, and particularly discloses a preparation method of a dexmedetomidine hydrochloride degradation impurity. The preparation method comprises the steps of carrying out oxidation reaction on dexmedetomidine and soluble perborate, and after the reaction is finished, extracting, drying, concentrating and purifying to obtain the degradation impurity A. Through a specific synthesis process, the degradation impurity A shown in the formula (I) with the purity being 98% or above and the yield being greater than 77% is prepared and can serve as a related substance reference substance, the problem of the impurity reference substance source in dexmedetomidine hydrochloride is solved, and the method is of great significance to quality control of dexmedetomidine hydrochloride and subsequent preparation research.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a preparation method for dexmedetomidine hydrochloride to degrade impurities. Background technique [0002] Dexmedetomidine hydrochloride, the dextro isomer of medetomidine, is a new type of highly selective α2-adrenoceptor agonist. Compared with medetomidine, dexmedetomidine hydrochloride has a stronger selectivity for central α2-adrenoceptor stimulation, and has a shorter half-life and a smaller dosage. Dexmedetomidine Hydrochloride Injection is jointly developed by OrionPharma (Finland) and Abott (USA). It was first launched in the US in March 2000, in Japan in January 2004, and in China in 2009. Clinically, it is mainly used for sedation of intubation and ventilator patients during intensive care treatment. Years of clinical experience at home and abroad have shown that dexmedetomidine hydrochloride injection has a strong sedative effect, especially has a unique psyc...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D233/64
CPCC07D233/64
Inventor 孙晓飞郭志强卢文娟谷洁琼
Owner HEBEI GUOLONG PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com